PB1844: REAL: A RETROSPECTIVE STUDY OF THE CLINICO-BIOLOGICAL FEATURES OF ACUTE MYELOID LEUKEMIA AND MYELODYSPLASTIC SYNDROMES PATIENTS INCLUDED IN AN EARLY PHASE TRIAL AT A COMPREHENSIVE CANCER CENTER.
Authors: Guillaume Berton, Cécile Vicier, Marie-Anne Hospital, Colombe Saillard, Yosr Hicheri, Valerio Maisano, Ferdinand Villetard, Camille Rouzaud, Evelyne D’incan Corda, Jerome Rey, Bilal Mohty, Aude Charbonnier, Aurelien Proux, Norbert Vey, Anthony Goncalves, Sylvain Garciaz
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: AML and high-risk MDS are aggressive diseases with poor response to standard therapies. Access to innovative therapies through the inclusions in early-phase clinical trials (EPCT) is possible in Comprehensive Cancer Centers. Retrospective data regarding AML/MDS patients included in EPCT is scarce. Aims: We performed a retrospective analyze of patients with AML/MDS included in a EPCT at the Institut Paoli-Calmettes (IPC) with a CLIP2 label from the French National Cancer Institute. Methods: This monocentric study included all the AML/MDS patients referred for a potential inclusion in an EPCT at IPC. Data were collected from patient electronic medical records. Results: Between Oct 2020 and Dec 2022, 114 AML/MDS patients were referred to the EPCT unit for a potential inclusion. One-hundred and two patients were screened, 65 (63.7%) were included and 37 (36.3%) were screen-failed. Reasons for non-inclusion were poor-general status in 8 patients (25.8%), biological abnormalities in 8 patients (25.8%), infection in 7 patients (22.6%), patient opposition in 5 patients (13.5%), progression in 2 patients (6.5%) and other reasons in 7 patients (18.9%). Thirteen patients (20%) were referred from other centers and 52 (80%) were treated at IPC prior to inclusion. Eleven patients (16.9%) were included in a front-line setting and 64 patients (83.1%) had relapsed/refractory (R/R) diseases. Forty-three (66%), 13 (20%) and 9 (14%) patients were included in a phase 1, 1/2 and 2 EPCT, respectively. Median age was 72 yo (22-85), PS score at inclusion was 1 (0-1). Nine patients (13.8%) had MDS and 56 patients (86.2%) had AML, including de novo, “Myelodysplasia related”, and “therapy related” AML in 36 (64.2%), 17 (30.4%) and 3 patients (5.4%), respectively. ELN 2022 prognostic risk was favorable, intermediate, and adverse for 8%, 29% and 63% of patients respectively. Median number of prior lines of therapy (LOT) was 2 (0-7). Thirty-one patients (47.7%) had been previously exposed to Azacitidine/Venetoclax and 16 (24.6%) patients had undergone prior allogeneic hematopoietic stem cell transplantation (allo-SCT). Investigational drugs were immunotherapy, small molecules, and new cytotoxic agents in 39 (60%), 18 (27.7%) cases and 8 (12.3%), respectively. Treatment related grade 3-4 adverse events was 27,7%. Twelve patients (18.5%), including 7 patients in the R/R group and 5 patients in the 1st line group achieved a complete response (CR) or a CR with incomplete hematological recovery (CRi). Composite complete remission (CRc) rate (including CR, PR and MLFS) was 27.7% (18 patients), including 10 patients (18.4%) in the R/R AML/MDS group, respectively. Median duration of treatment in the study was 49 days (ranges, 6-598). Reasons for study discontinuation were progression, unacceptable toxicity, allo-SCT, or patient decision in 35 (60.3%), 7 (12.1%), 4 (6.9%) and 1 (1.7%) case, respectively. Eleven patients died during the study (all the deaths were judged non-related to the investigational drugs by investigators). Overall Survival (OS) measured from the date of inclusion was 10 months (95%CI, 3.7-16.2) in the whole cohort and 5 months (95%CI, 0-10.9) in the R/R group of patients (Figure). R/R status at inclusion and number of prior LOT (≤ 2 vs > 2) were associated with lower CRc rate (p=0.004 and p=0.006 respectively). R/R status was predictive of worse survival in multivariate analysis (p=0.025, HR 4.98 [95% CI: 1.23-20.19]). Summary/Conclusion: AML/MDS patients enrolled in an EPCT program reached significant CRc response rate (27.7%) and median OS (10 months). Main determinants of efficacy were number of prior LOT and R/R status at inclusion.Keywords: MDS/AML, Acute myeloid leukemia, MDS, Phase I/II